Medications are indispensable in modern medicine. They save lives, alleviate discomfort, and improve the quality of life for many patients. However, what is often underestimated is their impact on hormone balance. In particular, testosterone levels can be significantly affected by various active ingredients.
A lowered testosterone level does not always manifest immediately and clearly. Typical symptoms include loss of libido, reduced performance, lack of drive, depressive mood, muscle loss, or an increase in body fat (Wu et al., 2010). Since these complaints are non-specific, the cause is often not suspected to be in the hormone balance. The connection with existing medication therefore often goes unrecognized.
The following article highlights which groups of medications can influence testosterone levels, what mechanisms are behind them, and why early hormonal monitoring is advisable.
How is testosterone regulated in the body? The HPG axis simply explained
To understand how medications can affect testosterone levels, it is helpful to know the natural hormonal control.
Testosterone production does not begin in the testes themselves, but in the brain. More precisely, in a small region called the hypothalamus. This structure functions as the body's central hormonal control center.
Step 1: The start in the brain
The hypothalamus releases a hormone called GnRH. This hormone is, so to speak, the starting signal for testosterone production.
Step 2: The relay to the pituitary gland
GnRH reaches the pituitary gland, where it causes the release of another hormone: LH, luteinizing hormone.
Step 3: Production in the testes
LH acts directly on the Leydig cells in the testes. These specialized cells then produce testosterone.
This three-stage regulation is referred to as the Hypothalamic-Pituitary-Gonadal axis, or HPG axis for short (Bhasin et al., 2018).
The principle of (negative) feedback
Additionally, a feedback mechanism exists:
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If testosterone levels in the blood rise, the brain registers this and reduces GnRH and LH secretion.
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If testosterone drops, production is stimulated again.
This finely tuned system normally ensures stable hormone levels (“Textbook of Endocrine Physiology,” 2011).
However, if one of these levels is disrupted by medication, stress, chronic illnesses, or other influences, the entire axis can become imbalanced. This is precisely where many of the active ingredients described below come into play.
Which medications can affect testosterone levels?
In addition to so-called androgen deprivation therapy, which, for example, in prostate cancer has the explicit medical goal of medically lowering testosterone levels, a variety of other active ingredients can also negatively influence testosterone levels as an undesirable side effect. Besides strong painkillers, the so-called opioids, antihypertensives (e.g. beta-blockers) or antidepressants (especially the group of selective serotonin reuptake inhibitors, so-called SSRIs) and antipsychotics can also affect testosterone levels. The extent of the influence varies individually and the mechanisms of action of the respective active ingredients differ. Furthermore, the duration of intake, age, weight, and concomitant diseases can play a role (Basaria, 2014).
This list already shows how broad the spectrum of potentially relevant medications is. This is particularly relevant for men with chronic illnesses, as multiple active ingredients are often used simultaneously.
Opioids and the inhibition of the HPG axis
Chronic pain patients who receive opioids for an extended period have a particularly high risk of hormonal suppression. These include, for example, active ingredients such as morphine, oxycodone, hydromorphone, fentanyl, tilidine, or tramadol. These medications are frequently used for chronic back pain, tumor pain, or neuropathic pain. The effect can occur after just a few weeks to months and is by no means rare in practice (Coluzzi et al., 2018).
Opioids lower testosterone levels by activating specific receptors in the hypothalamus, a special region in the brain that acts as the superior hormonal control center, and thereby inhibiting the hypothalamic-pituitary-gonadal axis or a consecutive reduction in the hormonal stimulation of the testes (Kafel et al., 2025).
Simply put, this means: Opioids not only relieve pain but also influence the hormonal control center in the brain. The signal chain from the hypothalamus via the pituitary gland to the testes is slowed down. As a result, the testes receive less stimulation for testosterone production (Daniell, 2002).
This so-called opioid-induced androgen deficiency is well described and can significantly impair libido, energy, muscle mass, and mood (Abs et al., 2000).
Typical complaints include fatigue, loss of libido, reduced strength, or depressive mood (Basaria et al., 2015). Since these symptoms also frequently occur in chronic pain patients, the hormonal component is not always recognized in practice. Targeted laboratory control can provide clarity here.
Antidepressants and serotonergic mechanisms
Antidepressants can also have hormonal effects.
Antidepressants such as the group of so-called SSRIs increase serotonergic activity and thus inhibit the GnRH-producing neurons and consequently hormone secretion in the pituitary gland; they can also indirectly increase prolactin levels by inhibiting dopamine-producing neurons (Corona et al., 2009).
This complex neuroendocrine interaction shows that the influence is not only direct on the testes but is mediated via central regulatory mechanisms in the brain. Especially with long-term use, hormonal involvement should therefore be considered in the presence of corresponding symptoms.
Antipsychotics and the influence via prolactin
Antipsychotics such as risperidone or haloperidol can increase prolactin levels and thus consequently lower testosterone levels (Molitch, 2005).
Prolactin inhibits the secretion of GnRH in the hypothalamus. As a result, LH and FSH from the pituitary gland decrease, which reduces the stimulation of the testosterone-producing Leydig cells in the testes. Testosterone production decreases. Clinically, this can manifest as loss of libido, erectile dysfunction, or fertility disorders (Holt & Peveler, 2010).
Glucocorticoids and direct effects on the testes
Cortisone preparations are used for many diseases, such as asthma, rheumatism, or autoimmune diseases.
Glucocorticoids (e.g., prednisolone or dexamethasone) can also suppress endogenous testosterone production by inhibiting the hypothalamic-pituitary-gonadal axis and also have a direct negative effect on the testosterone-producing cells in the testes. These effects come into play particularly with prolonged use or systemic therapy (Whirledge & Cidlowski, 2013).
Here, two mechanisms work simultaneously: The central control is dampened, and additionally, the Leydig cells in the testes can be directly affected.
Why is medication-induced testosterone deficiency often overlooked?
Medication-induced testosterone deficiency or the influence of various active ingredients on the hormonal control of testosterone production is well documented and pathophysiologically understood. However, the symptoms are often overlooked in clinical practice, or the information about them is often inadequate because the focus is on treating the underlying disease. It is therefore important to discuss the issue with patients and to carry out an early check of testosterone levels.
If you want to know how a testosterone test works and which values are important, read our article “Step-by-Step Guide to the Testosterone Test”.
In practice, the focus is understandably on the underlying disease. Fatigue or loss of libido are then often attributed to depression, pain syndrome, or age. Targeted laboratory control often only takes place late.
When should a hormonal clarification be carried out?
Hormonal diagnostics are advisable for:
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newly occurring loss of libido
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unexplained fatigue
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decrease in performance
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depressive symptoms
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long-term therapy with opioid pain relievers
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therapy with antipsychotics or SSRIs
Relevant laboratory parameters include:
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free testosterone
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possibly prolactin
It is important to interpret these in the clinical context. An isolated laboratory value without considering symptoms and comorbidities is not sufficient (MALE HYPOGONADISM - UROWeB, n.d.).
You can find more on the topic of testosterone deficiency in our article “Testosterone deficiency in men: Causes, symptoms, and solutions”.
Therapeutic considerations
It is not always possible or advisable to change medication. In some cases, a dose adjustment, a change of active ingredient, or supplementary hormonal therapy may be considered. This decision should always be made individually and interdisciplinarily.
Especially with long-term use of hormonally relevant medications, regular monitoring of endocrine parameters is recommended to detect creeping developments early.
Our conclusion, your knowledge
Medications can have a significant impact on male hormone balance. In addition to oncological therapies, opioids, antidepressants, antipsychotics, antihypertensives, and glucocorticoids are particularly relevant.
Medication-induced testosterone deficiency is well explained pathophysiologically but is often not sufficiently considered in clinical practice. Men with corresponding symptoms should therefore not hesitate to have their medication critically reviewed and, if necessary, to undergo hormonal clarification.
Open medical communication and targeted laboratory diagnostics are crucial to avoid long-term health consequences and maintain quality of life.
